Respiratory failure from acute respiratory distress syndrome (ARDS) is associated with high mortality acutely (up to 40%), and accounts for about 4 million ICU days annually in the U.S. ARDS survivors have substantial morbidity, and may have long-term physical and mental health impairments. ARDS imposes significant burdens on public health resources worldwide, and only minimal improvements in outcomes have occurred over recent decades.
Risks for developing ARDS include a diverse range of predisposing factors and initiating insults, such aspiration, pneumonia, trauma, sepsis, pancreatitis, inhalation injury, transfusion, and burns. Regardless of etiology, ARDS results in progressive deterioration in lung function towards a final common pathway: respiratory failure characterized by alveolar flooding, derecruitment, reduced compliance, increased shunting and dead space, and life-threatening hypoxemia. A key pathologic feature of ARDS is the heterogeneity of local injury severity and regional mechanical properties.
The mainstay of treatment for ARDS is endotracheal intubation and conventional mechanical ventilation (CMV). However CMV may exacerbate existing lung injury, due to cyclic, intratidal overdistention and repeated, asynchronous opening and closing of airways with each inflation. The mechanical stresses associated with these phenomena result in the release of cytokines and other inflammatory mediators that may exacerbate lung injury. This ventilator-associated lung injury (VALI) is thus a direct result of the mechanical heterogeneity of injured parenchyma, leading to maldistribution of ventilation and corresponding impairments in gas exchange.
Ventilation strategies that limit this end-expiratory derecruitment and end-inspiratory overdistension are the only interventions to have significantly reduced the morbidity and mortality of ARDS, using appropriate levels of positive end expiratory pressure (PEEP) to limit end-expiratory opening and closing and low tidal volumes (VT's) to reduce inspiratory overdistention. Such ‘protective’ ventilation strategies, however, may result in significant hypoventilation of the injured lung, due to increased deadspace and ventilation to perfusion ratio ({dot over (V)}/{dot over (Q)}) abnormalities. Most lung protective strategies for ventilator management use algorithmic, ‘one size fits all’ approaches, based on height, weight, or global arterial oxygenation. Adjustments to VT or PEEP based on such criteria provide little insight into how such interventions impact regional gas transport in the injured lung, or how to customize a ventilator management strategy for an individual patient's pathophysiology. For example, the optimal level of PEEP depends much more on the unique pattern of injury and amount of recruitable lung, rather than on oxygenation alone.
There is a continuing need for improvement in ventilation techniques to treat a variety of lung conditions and injuries.